Correction: The leptomeninges as a critical organ for normal CNS development and function: First patient and public involved systematic review of arachnoiditis (chronic meningitis).

[This corrects the article DOI: 10.1371/journal.pone.0274634.].

The leptomeninges as a critical organ for normal CNS development and function: First patient and public involved systematic review of arachnoiditis (chronic meningitis).

BACKGROUND & IMPORTANCE: This patient and public-involved systematic review originally focused on arachnoiditis, a supposedly rare "iatrogenic chronic meningitis" causing permanent neurologic damage and intractable pain. We sought to prove disease existence, causation, symptoms, and inform future directions. After 63 terms for the same pathology were found, the study was renamed Diseases of the Leptomeninges (DLMs). We present results that nullify traditional clinical thinking about DLMs, answer study questions, and create a unified path forward. METHODS: The prospective PRISMA protocol is published at Arcsology.org. We used four platforms, 10 sources, extraction software, and critical review with ≥2 researchers at each phase. All human sources to 12/6/2020 were eligible for qualitative synthesis utilizing R. Weekly updates since cutoff strengthen conclusions. RESULTS: Included were 887/14286 sources containing 12721 DLMs patients. Pathology involves the subarachnoid space (SAS) and pia. DLMs occurred in all countries as a contributor to the top 10 causes of disability-adjusted life years lost, with communicable diseases (CDs) predominating. In the USA, the ratio of CDs to iatrogenic causes is 2.4:1, contradicting arachnoiditis literature. Spinal fusion surgery comprised 54.7% of the iatrogenic category, with rhBMP-2 resulting in 2.4x more DLMs than no use (p<0.0001). Spinal injections and neuraxial anesthesia procedures cause 1.1%, and 0.2% permanent DLMs, respectively. Syringomyelia, hydrocephalus, and arachnoid cysts are complications caused by blocked CSF flow. CNS neuron death occurs due to insufficient arterial supply from compromised vasculature and nerves traversing the SAS. Contrast MRI is currently the diagnostic test of choice. Lack of radiologist recognition is problematic. DISCUSSION & CONCLUSION: DLMs are common. The LM clinically functions as an organ with critical CNS-sustaining roles involving the SAS-pia structure, enclosed cells, lymphatics, and biologic pathways. Cases involve all specialties. Causes are numerous, symptoms predictable, and outcomes dependent on time to treatment and extent of residual SAS damage. An international disease classification and possible treatment trials are proposed.

Spatiotemporal trends in teen birth rates in the USA, 2003-2012.

The objective of this analysis was to explore temporal and spatial variation in teen birth rates TBRs across counties in the USA, from 2003 to 2012, by using hierarchical Bayesian models. Prior examination of spatiotemporal variation in TBRs has been limited by the reliance on large-scale geographies such as states, because of the potential instability in TBRs at smaller geographical scales such as counties. We implemented hierarchical Bayesian models with space-time interaction terms and spatially structured and unstructured random effects to produce smoothed county level TBR estimates, allowing for examination of spatiotemporal patterns and trends in TBRs at a smaller geographic scale across the USA. The results may help to highlight US counties where TBRs are higher or lower and to inform efforts to reduce birth rates to adolescents in the USA further.

Hot spots, cluster detection and spatial outlier analysis of teen birth rates in the U.S., 2003-2012.

Teen birth rates have evidenced a significant decline in the United States over the past few decades. Most of the states in the US have mirrored this national decline, though some reports have illustrated substantial variation in the magnitude of these decreases across the U.S. Importantly, geographic variation at the county level has largely not been explored. We used National Vital Statistics Births data and Hierarchical Bayesian space-time interaction models to produce smoothed estimates of teen birth rates at the county level from 2003-2012. Results indicate that teen birth rates show evidence of clustering, where hot and cold spots occur, and identify spatial outliers. Findings from this analysis may help inform efforts targeting the prevention efforts by illustrating how geographic patterns of teen birth rates have changed over the past decade and where clusters of high or low teen birth rates are evident.

A nonterminal equine mandibular model of bone healing.

OBJECTIVES: To develop a nonterminal large animal bone defect model for assessing the efficacy of regenerative and pharmacologic treatments designed to enhance bone healing. STUDY DESIGN: In vivo experimental. SAMPLE POPULATION: Adult gelding horses (n = 6). METHODS: Under general anesthesia, using radiographic guidance, 13.5 mm diameter bilateral, full thickness mandibular defects were created in 6 horses using a custom surgical jig and coring bit. After 16 weeks, under general anesthesia, 23 mm diameter cores that encompassed the original healing defects and surrounding parent bone material were removed for evaluation. Oxytetracycline was administered 14 days before final core harvest to label bone-forming surfaces. Healing was qualitatively assessed from decalcified hematoxylin and eosin (H&E) stained and undecalcified fluorescent labeled sections. Trabecular to cortical bone fraction (Tb.V/Ct.V), bone volume fraction (BV/TV), tissue mineral density (TMD), and apparent bone mineral density (aBMD) were quantified using microcomputed tomography and compared between left and right sides using Wilcoxon signed rank test. RESULTS: BV/TV was not significantly different between left and right-sided defects. Bone deposition occurred centripetally from the border of the original defect, filling 67% ± 16% (SD) of the defect at 16 weeks. CONCLUSION: This model has potential use for comparison of regenerative and pharmacologic products aimed to augment bone healing.